Human insulin-like growth factor-1 (IGF-1) is a 7649-dalton polypeptide belonging to a family of somatomedins with insulin-like metabolic actions and the differentiative, mitogenic, and anti-apopototic biological activities that modulate the actions of growth hormone (GH). IGF-1 mediates the effects of GH on post-natal growth in humans. Like GH, IGF-1 is a potent anabolic protein. IGF-1 has hypoglycemic effects similar to those of insulin, and also promotes positive nitrogen balance. It is estimated that approximately 20,000 children in the United States have growth failure due to growth hormone deficiency and a large number have IGF-1 deficiency in the presence of normal GH secretion. In addition, a larger number of adults also have these hormone deficient states.
IGF-1 deficiency (IGFD) can be due to a resistance to GH action or as a result of GH deficiency (GHD). IGFD that is due to resistance to GH action is termed primary IGFD, while IGFD resulting from GHD is termed secondary IGFD. Currently, production of GH following administration of a GH secretagogue or of an agent that stimulates GH secretion is used as an indication of GHD. There is currently no single test that can distinguish between individuals having primary IGFD and secondary IGFD, or assign an appropriate therapy such as GH, IGF-1 or combination therapy of GH and IGF-1. As a result, many individuals may receive inappropriate or ineffective treatment.
Accordingly, there is a need in the art to improve the diagnosis of IGF-1 deficiency, and particularly a need for improved diagnostic methods that allow discrimination between primary IGFD and secondary IGFD, and to discover how responsive patients are to therapy with GH. Such diagnostics facilitate selection of therapies appropriate for the disease or disorder. Currently, IGF-1 deficiency is established on the basis of measuring blood IGF-1 levels and comparing them to the blood IGF-1 levels obtained from a large number of individuals to establish an IGF-1 standard deviation score (IGF-1 SDS).
The present invention addresses this need by providing, for example, improved methods of establishing that a patient is IGF-1 deficient not only based on their blood concentration of IGF-1 but also on their ability to produce IGF-1 both before and after their blood GH levels are increased. The invention also provides advantages related to such improved diagnostics.
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